ICAM-1 Antisense Oligonucleotide for Radiation Proctitis Treatment

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Solution Overview

Problem

Current treatments for Radiation Induced Proctitis, a side effect of pelvic radiation therapy, are inadequate, causing persistent bleeding, inflammation, and quality of life issues, with limited effectiveness of existing therapies like thermal therapy and medications.

Innovation Solution

A composition comprising an ICAM-1 antisense oligonucleotide with a specific nucleic acid sequence (SEQ ID NO:1) is used to treat Radiation Induced Proctitis, delaying, reducing, or ameliorating symptoms such as rectal bleeding, diarrhea, and pain, by specifically hybridizing to the 3′-untranslated region of human ICAM-1 mRNA, and can be administered via various routes including rectal enemas.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If thermal therapy is used to stop bleeding and inflammation, then the severity of symptoms is reduced, but the invasiveness and patient discomfort increase

Engineering Contradiction:
Improvesymptom severityVSAvoidpatient compliance
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The patent replaces mechanical thermal therapy with a biochemical mechanism using antisense oligonucleotides that bind to ICAM-1 mRNA to prevent protein synthesis, thereby treating radiation proctitis through molecular biology rather than thermal/mechanical intervention

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The antisense oligonucleotide acts as an intermediary molecule that specifically binds to ICAM-1 mRNA, preventing the translation of the ICAM-1 protein and thereby reducing inflammation and bleeding without requiring invasive thermal procedures

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If sucralfate, 5-ASA or corticosteroid enemas are used, then pain and inflammation are reduced, but the effectiveness is limited

Engineering Contradiction:
Improveinflammation and painVSAvoidtreatment effectiveness
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent extracts and targets the specific molecular cause of radiation proctitis by designing an antisense oligonucleotide that specifically binds to ICAM-1 mRNA, removing the pathogenic mechanism at its source rather than providing general anti-inflammatory coverage

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The antisense oligonucleotide provides localized and specific action at the molecular level by binding exclusively to ICAM-1 mRNA sequences, creating a targeted therapeutic effect that addresses the specific pathogenic mechanism without the broad, less effective coverage of conventional enemas

Inventive Principle:
Principle #3Local quality

3Object-affected harmful factors

If multiple thermal therapy treatments are required, then the bleeding and inflammation are controlled, but the treatment complexity and patient burden increase

Engineering Contradiction:
Improvebleeding and inflammation controlVSAvoidtreatment protocol complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The antisense oligonucleotide is administered in advance to prevent the expression of ICAM-1 protein, thereby preventing the development of radiation proctitis symptoms before they occur, rather than requiring multiple subsequent treatments to control established symptoms

Inventive Principle:
Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The oligonucleotide effectively reduces inflammation, pain, and discharge associated with Radiation Induced Proctitis, offering a therapeutically effective treatment option with potential for long-term symptom remission and improved patient compliance.

Implementation Method 1

SEQ ID NO:1 is a 20-base phosphorothioate oligodeoxynucleotide designed to specifically hybridize to a sequence in the 3′-untranslated region of the human ICAM-1 mRNA

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS10059948B2Antisense treatment of radiation induced diseases in the gastrointestinal tract
Publication Date: 2018.08.28 ATLANTIC PHARMA HLDG

AI summary

This invention relates to a composition comprising an antisense oligonucleotide for use in treating radiation induced disease of the gastrointestinal tract.